Influenza viruses have on their surfaces two biologically active glycoproteins, a hemagglutinin and a neuraminidase. The object of this proposal is to determine how these two viral components interact with host cells and to thereby elucidate their roles in virus replication. Specifically, we intend to identify and characterize the viral receptors on host cells using a variety of techniques including direct binding studies, the isolation of host cell variants with altered membrane components, and the isolation of the receptors by affinity chromatography. In addition we will use in vitro modification of the virion glycoproteins, growth of the virus cells with altered membranes, and the formation of liposomes containing viral glycoproteins to determine which structural and chemical properties of the viral envelope are required for binding the virus to cells and for initiation of infection. We will investigate the role of soluble glycoprotein hemagglutination inhibitors in the infectious process and will study their effects on binding of the virus to host cells. Using appropriate mutants and precursors of the viral glycoproteins we will determine whether viral neuraminidase is indeed responsible for removing sialic acid residues from the virion glycoproteins or whether these molecules fail to accept sialic acid from host cell sialytransferases. Finally, we will investigate the effects of sialylation and other in vitro induced viral alterations on the infectivity of virus introduced into the respiratory tract and on the circulation time of virus put into the blood stream. The experiments are aimed at acquiring information about mechanisms of virus attachment and penetration which can be of use in controlling the replication of the virus in nature.